2. Academic Validation
  3. Identification of a novel class of androgen receptor antagonists based on the bicyclic-1H-isoindole-1,3(2H)-dione nucleus

Identification of a novel class of androgen receptor antagonists based on the bicyclic-1H-isoindole-1,3(2H)-dione nucleus

  • Bioorg Med Chem Lett. 2005 Jan 17;15(2):389-93. doi: 10.1016/j.bmcl.2004.10.051.
Mark E Salvati 1,  Aaron Balog,  Donna D Wei,  Dacia Pickering,  Ricardo M Attar,  Jieping Geng,  Cheryl A Rizzo,  John T Hunt,  Marco M Gottardis,  Roberto Weinmann,  Rogelio Martinez
Affiliations

Affiliation

  • 1 Department of Oncology Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. [email protected]
PMID: 15603960 DOI: 10.1016/j.bmcl.2004.10.051
Abstract

A novel series of isoindoledione based compounds were identified as potent antagonists of the Androgen Receptor (AR). SAR around this series revealed dramatic differences in binding and function in mutant variants (MT) of the AR as compared to the wild type (WT) receptor. Optimization of the aniline portion revealed substitution patterns, which yielded potent antagonist activity against the WT AR as well as the MT AR found in the LNCaP and PCa2b human prostate tumor cell lines.

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